Jason's post is technically correct in terms of what leap does and how it
is not particularly "smart" about building missing atoms. Nonetheless, in
my experience leap can more than adequately mutate nucleobases, except
perhaps pyridine to purine substitutions. I have routinely done A to G, U
to C, and C to U mutations with great success. One need only delete
exocyclic atoms (e.g. N4 of cytosine) and change the residue name. 500 to
1000 cycles of minimization and then some brief dynamics with backbone
heavy atom restraints has, in my experience, been more than enough to
generate stable trajectories of the mutants.
Regards,
Brian
On Sat, Mar 8, 2014 at 11:02 AM, Debayan Chakraborty
<debayan.ch.gmail.com>wrote:
> I think the 3DNA code (http://x3dna.org/) has scripts which will help you
> do the mutations (for both DNA as well as RNA). It generates a pdb file for
> the mutated sequence, and you can convert that to a format that leap
> understands.
>
> Debayan
>
>
> On Sat, Mar 8, 2014 at 3:20 PM, Jason Swails <jason.swails.gmail.com>
> wrote:
>
> > On Sat, Mar 8, 2014 at 2:14 AM, Raviprasad Aduri <
> > aduri.goa.bits-pilani.ac.in> wrote:
> >
> > > Dear All,
> > >
> > > I am looking for some help on mutating residues in a RNA hairpin and
> then
> > > energy minimizing the structure using AMBER. Given a PDB file, is it
> > > possible to mutate a residue (say A to G) in AMBER and then carry out
> > > energy minimization to see how that mutation effects the structure.
> > >
> >
> > Amber has only very basic mutation capabilities. The tleap/xleap
> > programs will automatically add atoms that are missing from any residues
> in
> > the input PDB file. This is frequently used to fill in hydrogen atoms
> that
> > are missing from X-ray crystallographic structures (whose resolution is
> too
> > low to resolve hydrogen locations).
> >
> > This functionality can be leveraged to mutate structures, but it has some
> > potentially severe drawbacks. If you change the residue name from A to G
> > for a particular residue in your input PDB structure, leap will model
> that
> > residue as a G instead of an A. In order to do this, though, you need to
> > delete all atoms that are present only in an Adenine (since otherwise you
> > will get complaints from tleap about unrecognized atoms in the residue).
> > However, tleap is not very intelligent about where it adds missing atoms
> > and simply adds them based on their positions in that residue's template.
> >
> > As a result, I suggest keeping as many atoms from the 'old' residue that
> > are in the same location in the 'new' residue. You may have to rename
> some
> > of the atoms to reflect their atom names in the new residue (names should
> > follow the PDB standard). This approach minimizes the number of atoms
> that
> > leap has to add, and will likely result in better starting structures.
> >
> > HTH,
> > Jason
> >
> > --
> > Jason M. Swails
> > BioMaPS,
> > Rutgers University
> > Postdoctoral Researcher
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
================================ Current Address =======================
Brian Radak : BioMaPS
Institute for Quantitative Biology
PhD candidate - York Research Group : Rutgers, The State
University of New Jersey
University of Minnesota - Twin Cities : Center for Integrative
Proteomics Room 308
Graduate Program in Chemical Physics : 174 Frelinghuysen Road,
Department of Chemistry : Piscataway, NJ
08854-8066
radak004.umn.edu :
radakb.biomaps.rutgers.edu
====================================================================
Sorry for the multiple e-mail addresses, just use the institute appropriate
address.
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Received on Sun Mar 09 2014 - 13:00:02 PDT
